CN100345590C - Lozenge containing liver cell growth promoting agent and interferon - Google Patents
Lozenge containing liver cell growth promoting agent and interferon Download PDFInfo
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- CN100345590C CN100345590C CNB031541577A CN03154157A CN100345590C CN 100345590 C CN100345590 C CN 100345590C CN B031541577 A CNB031541577 A CN B031541577A CN 03154157 A CN03154157 A CN 03154157A CN 100345590 C CN100345590 C CN 100345590C
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- interferon
- hepatocyte growth
- promoting factors
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- 102000014150 Interferons Human genes 0.000 title claims abstract description 31
- 229940079322 interferon Drugs 0.000 title claims abstract description 31
- 239000003795 chemical substances by application Substances 0.000 title claims description 7
- 230000010261 cell growth Effects 0.000 title description 2
- 210000005229 liver cell Anatomy 0.000 title 1
- 239000007937 lozenge Substances 0.000 title 1
- 230000001737 promoting effect Effects 0.000 title 1
- 210000003494 hepatocyte Anatomy 0.000 claims abstract description 34
- 238000010521 absorption reaction Methods 0.000 claims abstract description 14
- 239000006189 buccal tablet Substances 0.000 claims abstract description 14
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
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- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
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- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 claims description 2
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Abstract
The present invention relates to a medical preparation of a buccal tablet containing a hepatocyte growth-promoting factor and interferon, every 100 grams of which comprises: 0.02 to 20% of hepatocyte growth-promoting factor, 104 to 107IU of interferon, 40 to 99.8% of bulking agent, 0.05 to 30% of stabilizing agent, 0 to 30% of absorption enhancer, 0 to 20% of taste modifying agent and 0 to 25% of pH value buffer. The buccal tablet has good synergistic treatment effect on treating liver disease, and the effective ingredient of the buccal tablet has the advantages of good stability, easy use by buccal absorption and easy absorption in the oral mucosa.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of especially pharmaceutical preparation of the buccal absorption that comprises hepatocyte growth-promoting factors and interferon of hepatitis B of hepatic disease for the treatment of.
Background technology
Still do not having specific medicament in treatment aspect the hepatitis B at present, often sb.'s illness took a turn for the worse serve as to treat emphasis to protect the liver and to prevent clinically.
Hepatocyte growth-promoting factors (Hepatocyte Growth Factor, be called for short HGF) be a kind of can the synthetic polypeptides matter of cell cultured supernatant DNA, be called hepatocyte growth factor, hepatic cell growth stimulating factor etc. again, normally obtain from animal livers (as the piglets liver) extraction and the production of genetic engineering recombination method.Hepatocyte growth-promoting factors (HGF) is at aspect determined curative effects such as treatment hepatitis, hepatic injury and hepatic fibrosis, because the oral meeting of HGF is destroyed its biological activity by digestive enzyme, influence therapeutic effect, the HGF that uses clinically all is injections at present, and patient especially chronic patients life-time service is very inconvenient.
Interferon is a kind of widely used clinically biologics with broad-spectrum antiviral, antitumor and immunoloregulation function, be divided into α, β and γ three classes by its antigenicity difference, and alpha-interferon has the hypotype more than 20, as Intederon Alpha-2a, Alfacon-1 b and Interferon Alpha-2b etc., beta-interferon has 4 hypotypes, and gamma interferon has 1 hypotype.What use clinically at present, mainly is alpha-interferon.
Chinese invention patent application number 95101216.9 and 98105384.X disclose the buccal tablet technology of interferon and thymosin and interleukin respectively; though these two technology have better action in the hepatopathy control; but its effective component all is based on the raising autoimmune, seriously is badly in need of recovering liver function and protects hepatocellular patient's therapeutic efficiency more single those hepatocyte are impaired.
Summary of the invention
The purpose of this invention is to provide a kind of pharmaceutical preparation that comprises hepatocyte growth-promoting factors and interferon that absorbs by buccal; it can finely keep the active and through port transmucosal of HGF and interferon to absorb the effect that reaches the treatment hepatic disease; the protection hepatocyte is not only arranged, recover liver function, regulate immunity and antiviral synergism, and easy to use in addition, be easy to be accepted and advantage such as compliance is good by the patient.
The solution that the present invention adopts is: hepatocyte growth-promoting factors and interferon are made buccal tablet, make it be easy to dissolve and discharge HGF and the absorption of interferon through port transmucosal under the effect of saliva of buccal cavity.
The concrete component design of the present invention and per 100 gram content are:
Hepatocyte growth-promoting factors 0.02～20%, interferon 10
4～10
7IU, filler 40～99.8%, stabilizing agent 0.05～30%, absorption enhancer 0～30%, taste modifying agent 0～20%, pH value buffer agent 0～25%.
Should be noted that, filler is the pharmaceutic adjuvant that is used for diluting and absorb hepatocyte growth-promoting factors and interferon, is convenient to bind compression molding and is easy to dissolve in the oral cavity, selects one or more combinations in starch, starch slurry, dextrin, mucialga of arabic gummy, gelatine size, Icing Sugar, lactose, the Polyethylene Glycol for use;
Function of stabilizer is to be used for protecting hepatocyte growth-promoting factors and interferon stable existence and avoid reducing its active pharmaceutic adjuvant in the medicine storage life, selects one or more combinations in lysine, arginine, glutamic acid, histidine, glycine, hetastarch, hydroxymethyl starch, low molecular dextran, mannitol, sorbitol, xylitol, sodium chloride, glucose and the polyvidon for use;
Absorption enhancer has and promotes the absorption in oral mucosa of hepatocyte growth-promoting factors and interferon, suppresses the oral mucosa endoenzyme, prevents that hepatocyte growth-promoting factors and interferon are by the effect of enzyme hydrolysis in the oral mucosa, absorption enhancer is selected one or more combinations in sodium laurylsulfate, sodium deoxycholate, aprotinin, propylene glycol, azone, menthol, bacitracin, NaGC, the sodium salicylate for use, absorption enhancer in containing slice prescription available also can, when its content is 0, represent without this composition;
The taste modifying agent is to improve the flavouring quality of medicine when containing to be convenient to the happy pharmaceutic adjuvant of accepting and using of patient, select one or more combinations in menthol, Borneolum Syntheticum, cyclamate, glycyrrhizin, the citric acid for use, the taste modifying agent in containing slice prescription available also can, when its content is 0, represent without this composition;
The pH value buffer agent is to regulate buccal tablet dissolve back pH value in the oral cavity variation, selects a kind of or its combination in phosphate, the citrate for use, the pH value buffer agent in containing slice prescription available also can, when its content is 0, represent without this composition.
Should be noted that, absorption enhancer in hepatocyte growth-promoting factors of the present invention and the inf oral tablet, taste modifying agent and pH value buffer agent can exist simultaneously or not be present in the drug formulation of buccal tablet, also can be in wherein a kind of drug formulation that is present in buccal tablet.
Should be noted that simultaneously, not only comprise the hepatocyte growth-promoting factors and the interferon of the various molecular weight of producing by biological extraction or genetic engineering as the hepatocyte growth-promoting factors in the troche of the present invention and interferon, also comprise the chemical modification body of acceptable hepatocyte growth-promoting factors and interferon on the medicine.
In addition, it will be appreciated by those skilled in the art that the manufacture method of hepatocyte growth-promoting factors of the present invention and inf oral tablet is similar to conventional medicine tablet manufacture method, repeats no more here.
Because hepatocyte growth-promoting factors of the present invention and inf oral tablet adopt above-mentioned formula system, not only aspect the treatment hepatic disease good synergistic therapeutic action is being arranged, and it is easy to use to suck absorption, be easy to oral mucosa and absorb.
The specific embodiment
Embodiment 1. gets hepatocyte growth-promoting factors 30 gram, and (α-2b) 2 * 10 for interferon
6IU, lysine 80 grams, lactose 900 grams, Icing Sugar 380 grams, starch slurry (17%) 1000 gram, manufacture method is as follows:
Earlier with stand-by after 30 gram hepatocyte growth-promoting factorss and 80 gram lysines and 50 gram starch slurry mix homogeneously granulations, the cold drying.
With 2 * 10
6The starch slurry mix homogeneously of IU Interferon Alpha-2b, 900 gram lactose, 380 gram Icing Sugar, 950 grams, granulation, cold drying.With two kinds of abundant mixings of granule, tabletting promptly makes every weight at 0.3 gram, detects packing and gets final product again.
Embodiment 2. adds 55 gram menthols in the composition of embodiment 1.
Earlier with stand-by after 30 gram hepatocyte growth-promoting factorss and 80 gram lysines and 50 gram starch slurry mix homogeneously granulations, the cold drying.
With 55 gram menthols, 2 * 10
6The starch slurry mix homogeneously of IU interferon, 900 gram lactose, 380 gram Icing Sugar, 950 grams, granulation, cold drying. with two kinds of abundant mixings of granule, tabletting promptly makes the hepatocyte growth factor and the inf oral tablet of Herba Menthae taste again.
Embodiment 3. gets hepatocyte growth-promoting factors 70 gram, and (α-2a) 4 * 10 for interferon
6IU, hetastarch 190 grams, sodium laurylsulfate 95 grams, starch 1500 grams, dextrin 210 grams, Icing Sugar 220 grams, 800 milliliters of 0.01M phosphate buffer aqueous solutions (PH=5.5).
Earlier hepatocyte growth-promoting factors, interferon, hetastarch, sodium laurylsulfate are dissolved in respectively in 800 ml phosphate buffers and make mixed solution, mixing is stand-by.Again starch, dextrin, Icing Sugar are mixed into uniform powder, then mixed solution are sprayed in mixed-powder, stir, tabletting after granulation, the cold drying makes every weight at 0.2 gram, detects packing and gets final product.
Claims (4)
1. the buccal tablet that comprises hepatocyte growth-promoting factors and interferon is characterized in that the each component and the content thereof of per 100 gram buccal tablet medicines is as follows: hepatocyte growth-promoting factors 0.02～20%, interferon 10
4～10
7IU, filler 40～99.8%, stabilizing agent 0.05～30%, absorption enhancer 0～30%, taste modifying agent 0～20%, pH value buffer agent 0～25%.
2. the buccal tablet that comprises hepatocyte growth-promoting factors and interferon according to claim 1 is characterized in that: filler is selected one or more combinations in starch, starch slurry, dextrin, mucialga of arabic gummy, gelatine size, Icing Sugar, lactose, the Polyethylene Glycol for use; Stabilizing agent is selected one or more combinations in lysine, arginine, glutamic acid, histidine, glycine, hetastarch, hydroxymethyl starch, low molecular dextran, mannitol, sorbitol, xylitol, sodium chloride, glucose and the polyvidon for use; Absorption enhancer is selected one or more combinations in sodium laurylsulfate, sodium deoxycholate, aprotinin, propylene glycol, azone, menthol, bacitracin, NaGC, the sodium salicylate for use; The taste modifying agent is selected one or more combinations in menthol, Borneolum Syntheticum, cyclamate, glycyrrhizin, the citric acid for use; The pH value buffer agent is selected a kind of or its combination in phosphate, the citrate for use.
3. according to claim 1, the 2 described buccal tablets that comprise hepatocyte growth-promoting factors and interferon, described hepatocyte growth-promoting factors comprises the hepatocyte growth-promoting factors of the various molecular weight of producing by biological extraction or genetic engineering.
4. according to claim 1, the 2 described buccal tablets that comprise hepatocyte growth-promoting factors and interferon, described interferon comprises the interferon of the various molecular weight of producing by biological extraction or genetic engineering, the interferon of each hypotype of α, β and γ three interferoids.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031541577A CN100345590C (en) | 2003-08-14 | 2003-08-14 | Lozenge containing liver cell growth promoting agent and interferon |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031541577A CN100345590C (en) | 2003-08-14 | 2003-08-14 | Lozenge containing liver cell growth promoting agent and interferon |
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| CN1513550A CN1513550A (en) | 2004-07-21 |
| CN100345590C true CN100345590C (en) | 2007-10-31 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110033556A1 (en) * | 2009-08-07 | 2011-02-10 | Zheming Jin | Natural Pharmaceutical Preparations for Increasing Albumin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1227124A (en) * | 1998-02-25 | 1999-09-01 | 上海华晨生物技术研究所 | Beta interferon lozenge and its preparing method |
| CN1367703A (en) * | 1999-05-31 | 2002-09-04 | 三菱化学株式会社 | Freeze dried HGF preparations |
-
2003
- 2003-08-14 CN CNB031541577A patent/CN100345590C/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1227124A (en) * | 1998-02-25 | 1999-09-01 | 上海华晨生物技术研究所 | Beta interferon lozenge and its preparing method |
| CN1367703A (en) * | 1999-05-31 | 2002-09-04 | 三菱化学株式会社 | Freeze dried HGF preparations |
Non-Patent Citations (2)
| Title |
|---|
| 促肝细胞生长素联合α_Lb干扰素治疗慢性活动性肝炎30例疗效观察 邱迎红等，黑龙江医药科学，第22卷第3期 1999 * |
| 干扰素与促肝细胞生长素联合治疗重症肝炎50例 张进化，苏州医学院学报，第19卷第9期 1999 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110033556A1 (en) * | 2009-08-07 | 2011-02-10 | Zheming Jin | Natural Pharmaceutical Preparations for Increasing Albumin |
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|---|---|
| CN1513550A (en) | 2004-07-21 |
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